The idiopathic interstitial pneumonias (IIPs) represents a class of chronic pulmonary fibrotic disorders characterized by progressive scarring of the alveolar interstitium leading to severe dyspnea, hypoxemia, and death. Among interstitial lung disease idiopathic pulmonary fibrosis (IPF) is the most progressive disease with median survival of 2.5-3 years (ATS/ERS. Am J Respir Crit Care Med 2002: 165(2): 277-304). Patients diagnosed with IPF typically experience progressive pulmonary insufficiency, and most die of respiratory failure. The ratio of the estimated prevalence (90,000 individuals) and incidence (30,000 individuals) of IPF in the United States reflects this poor prognosis (Raghu G, Weycker D, Edelsberg J, Bradford W Z, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006: 174(7): 810-816). The clinical course of IPF is highly variable and may be characterized by periods of relative stability, chronic decline, or periods of rapid decline (known as acute exacerbations).
Clinical and physiological parameters (e.g., forced vital capacity, diffusing capacity of carbon monoxide DLco, six minute walk test distance) are currently used to monitor disease state and progression. These clinical assessments of IPF and risk prediction models that incorporate these components (or change therein) are relatively successful in staging patients and predicting risk of mortality. However, management approaches that are based on molecular information (such as that derived from protein markers) may enable better monitoring of disease progression and risk of progression in patients with IPF.
There is a need in the art for well-defined biomarkers to determine if a patient has or is at risk for developing a fibrotic pulmonary disease, to indicate the progressiveness of the disease, and/or to facilitate evaluation of responsiveness to therapy. The invention provided herein addresses these and other needs in the art by providing, inter alia, novel protein biomarkers of fibrotic pulmonary diseases (e.g. IPF).